1.Analysis of changes and influencing factors of activation rate of peripheral blood monocytes after liver transplantation
Yu GONG ; Hui WU ; Jie ZHU ; Ting WANG ; Xiaowu HUANG
Chinese Journal of Clinical Medicine 2025;32(1):101-107
Objective To analyze the effect of the activation rate of peripheral blood monocytes on the recovery of patients after liver transplantation and to initially explore the possible influencing factors for differences in monocyte activation rates. Methods A total of 139 patients who underwent orthotopic liver transplantation from September 2020 to June 2023 at Department of Liver Surgery and Transplantation of Zhongshan Hospital, Fudan University were selected. The proportion of CD14+HLA-DR+ monocytes in peripheral blood was defined as the monocyte activation rate. The difference in monocyte activation rates between postoperative day 7 (POD7) and postoperative day 1 (POD1) was calculated as Δ, and patients were divided into Δ>0 group (n=73) and Δ<0 group (n=66). The two groups were compared in terms of complete blood count, liver and kidney function, coagulation indicators, infection indicators, ICU length of stay, total length of hospitalization, and 90-day mortality. Changes in the proportions of different monocytes subsets (Mo0, Mo1, Mo2, and Mo3) and HLA-DR expression in peripheral blood on POD1 and POD7 were detected using flow cytometry. Results The ICU length of stay in the Δ<0 group was significantly longer than that in the Δ>0 group (18[12, 26] days vs 14[10, 20.5] days, P=0.018). On POD1, the proportion of Mo0 in the Δ>0 group was significantly lower than that in the Δ<0 group (P<0.05); on POD7, the proportion of Mo0 in the Δ>0 group was significantly lower than that in the Δ<0 group (P<0.001), while the proportions of Mo1, Mo2, and Mo3 were significantly higher than those in the Δ<0 group (P<0.001). Compared to POD1, the HLA-DR expression level of Mo0 in peripheral blood of patients with liver transplantation significantly decreased on POD7 (P<0.01), while there was no significant difference in HLA-DR expression levels of Mo1, Mo2, and Mo3. Conclusions Increased proportion of Mo0 (CD14lowCD16−HLA-DRlow) among peripheral blood monocyte subsets may be one of the influencing factors for the differences in monocyte activation rates in patients with liver transplantation. The difference in monocyte activation rate can serve as a new clinical indicator for assessing changes in the immune status and postoperative recovery of patients with liver transplantation.
2.DiPTAC: A degradation platform via directly targeting proteasome.
Yutong TU ; Qian YU ; Mengna LI ; Lixin GAO ; Jialuo MAO ; Jingkun MA ; Xiaowu DONG ; Jinxin CHE ; Chong ZHANG ; Linghui ZENG ; Huajian ZHU ; Jiaan SHAO ; Jingli HOU ; Liming HU ; Bingbing WAN ; Jia LI ; Yubo ZHOU ; Jiankang ZHANG
Acta Pharmaceutica Sinica B 2025;15(1):661-664
3.TransTACs: Transforming antibodies into targeted protein degraders.
Yu GUO ; Jinxin CHE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(2):1186-1188
4.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.
5.Quality re-optimization and assessment of radiotherapy plan for rectal cancer
Lin HUANG ; Yimei LIU ; Meining CHEN ; Shaomin HUANG ; Xiaowu DENG ; Yinglin PENG ; Yu ZHANG
Chinese Journal of Medical Physics 2024;41(2):133-138
Objective To evaluate the quality of treatment planning(TP)and re-optimization planning(RP)of radiotherapy for rectal cancer using PlanIQ software,thereby providing methods and tools for the screening and optimization of radiotherapy plans.Methods Twenty patients with rectal cancer who received radiotherapy were selected retrospectively,with 10 cases of intensity-modulated radiotherapy(IMRT)and 10 of volumetric modulated arc therapy(VMAT).(1)TP:IMRT plan involved 5-field irradiation,and VMAT plan involved two 360°arcs.The prescription doses were 50 Gy/25 f for PTV1 and 45 Gy/25 f for PTV2.All plans underwent direct machine parameter optimization and required 95%isodose lines to cover 100%of the target volume.Organs-at-risk(OAR)were limited by reference to tolerated dose standards.After the planning was completed,the plans were reviewed and confirmed by a physician,and the treatment was implemented after dose verification.(2)RP:a physicist with 10 years of experience re-optimized the 20 TP plans,with the irradiation technique and field setting unchanged.The re-optimization involved adjusting planning conditions and parameters based on individual experience until the dose to OAR was minimized while without affecting PTV coverage.The quality of TP plans and RP plans were quantitatively evaluated using PlanIQ software.Non-parametric Wilcoxon signed rank test was performed for dose-volume histogram parameters and plan quality index between two groups.Results The dose-volume histogram parameters in RP plans were superior to those in TP plans,and the differences in the Dmax of PTV1,the V45 Gy and Dmax of small intestine,and the V45 Gy of colon were statistically significant(P<0.05).The quality scores of RP plans for IMRT group,VMAT group and all patients were significantly higher than those of TP plans(P<0.05),with plan quality index of 88.55±3.35 vs 86.61±4.63(P=0.005),89.72±3.15 vs 87.21±3.04(P=0.028),and 89.14±3.22 vs 86.91±3.22(P=0.001),respectively.Conclusion RP can further improve the quality of radiotherapy plan for rectal cancer.PlanIQ software serves as an effective tool for quality control and screening of radiotherapy planning.
6.Application of intraoperative ultrasound in robot-assisted precise resection of pancreatic tumors
Zheng LI ; Wensheng LIU ; Qifeng ZHUO ; Yihua SHI ; Shunrong JI ; Xianjun YU ; Xiaowu XU
Chinese Journal of General Surgery 2024;33(9):1368-1376
The incidence and detection rates of benign and low-grade malignant pancreatic tumors have risen yearly.For patients with such tumors,traditional radical resection procedures often result in excessive loss of normal pancreatic parenchyma,leading to complications such as postoperative insufficiency of both exocrine and endocrine functions.Studies have shown that functional-preserving surgeries,such as minimally invasive enucleation or partial resection surgeries,can maximize the protection of patients'pancreatic function and improve long-term quality of life.However,for some tumors deep within the pancreatic parenchyma,accurately locating the tumor and protecting the pancreatic duct pose challenges.Intraoperative ultrasound(IOUS)has become an ideal intraoperative imaging tool,often referred to as the surgeon's"third eye"because of its portability,ability to provide real-time high-resolution information,non-reliance on ionizing radiation,and the fact that it does not require special patient preparation.With advancements in technology,the application scope of IOUS has expanded beyond its initially limited diagnostic role to various surgical applications,including identifying non-palpable lesions,guiding surgical strategies,and staging tumors.In the current era of minimally invasive and precision surgery,the proficiency of surgeons in using IOUS has become an important issue.This article reviews the history of IOUS applications,summarizes the advantages and basic usage methods of robotic IOUS,and shares techniques for applying IOUS in robot-assisted precise resection of pancreatic tumors.
7.Optimized arterial perfusion strategy in total arch replacement for acute type A aortic dissection with malperfusion syndrome
Xi LIN ; Hao YU ; Xianyue WANG ; Ben ZHANG ; Tao YAN ; Xiaowu WANG ; Tao MA ; Weida ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(04):467-472
Objective To investigate the effect of optimized arterial perfusion strategy on total arch replacement for acute type A aortic dissection (AAAD) with malperfusion syndrome (MPS). Methods From 2017 to 2019, 51 patients with AAAD and MPS who had received total arch replacement with optimized arterial perfusion strategy in our hospital were included in the optimized perfusion group, including 40 males and 11 females, with an average age of 47.43±13.39 years. A total of 40 patients with AAAD and MPS who had been treated with traditional Sun's surgery were taken as the traditional control group, including 31 males and 9 females, with an average age of 50.66±12.05 years. The perioperative clinical data of the two groups were compared. Results The preoperative baseline data of the two groups were basically consistent (P>0.05). The comparison of operative data between the optimized perfusion group and the traditional control group showed that in the optimized perfusion group, the extracorporeal circulation time, aortic occlusion time, and circulation-out cerebral perfusion time were significantly less than those in the traditional control group (223.64±65.13 min vs. 266.77±87.04 min, 114.48±27.28 min vs. 138.20±39.89 min, 8.28±3.81 min vs. 50.53±23.60 min, all P≤0.05). The lowest intraoperative nasopharyngeal temperature in the optimized perfusion group was significantly higher than that in the traditional control group (27.10±1.18℃ vs. 23.6±3.30℃, P=0.000). Postoperative wakefulness time of the optimized perfusion group was earlier than that of the traditional control group (4.50±1.35 h vs. 5.27±1.15 h, P=0.019). The volume of blood transfusions in the optimized perfusion group was significantly less than that in the traditional control group (13.25±9.06 U vs. 16.95±7.53 U, P=0.046). There was no significant difference in ICU time and invasive ventilation time between the two groups (P>0.05). Postoperative complications of the two groups showed that the incidence of postoperative continuous renal replacement therapy in the optimized perfusion group was significantly lower than that in the traditional control group, with a statistically significant difference (21.6% vs. 42.5% P=0.003). The incidence of postoperative delirium, coma, low cardiac row syndrome and limb ischemia in the optimized perfusion group was lower than that in the traditional control group, but the difference was not statistically significant (P>0.05). The incidence of postoperative hemiplegia, sepsis, and secondary thoracotomy in the optimized perfusion group was higher than that in the traditional control group, and the difference was not statistically significant (P>0.05). Postoperative mortality in the optimized perfusion group was significantly lower than that in the traditional control group (13.7% vs. 27.5%), but the difference was not statistically significant (P=0.102). Conclusion Optimized arterial perfusion strategy and its related comprehensive surgical technique reduce surgical trauma, shorten the operation time, reduce perioperative consumption of blood products. Postoperative wakefulness is rapid and the incidence of complications of nervous system, kidney and limb ischemia is low. Optimized arterial perfusion strategy is suitable for operation of AAAD with MPS by inhibiting the related potential death risk factors to reduce operation mortality.
8.Minimally invasive enucleation for benign and low-grade malignant pancreatic tumors: an analysis of 60 cases
Mengqi LIU ; Wensheng LIU ; Zheng LI ; Qifeng ZHUO ; Shunrong JI ; Wenyan XU ; Yihua SHI ; Xianjun YU ; Xiaowu XU
Chinese Journal of Surgery 2022;60(7):674-679
Objective:To investigate the safety and feasibility of minimally invasive pancreatic tumor enucleation.Methods:The clinicopathological data of 60 patients with minimally invasive pancreatic tumor enucleation admitted to the Department of Pancreatic Surgery of Fudan University Cancer Center from November 2019 to August 2021 were retrospectively analyzed. There were 17 males and 43 females,with age of (50.0±13.2)years(range: 23 to 73 years). Tumors were located in the head of pancreas in 40 cases(66.7%),neck and tail of pancreas in 20 cases(33.3%). Patients were divided into robotic group( n=25) and laparoscopic group( n=35) according to surgical methods. The measurement data were compared by t-test or Mann-Whitney U test, and the categorical data were compared by χ 2 test or Fisher exact probability method. The influencing factors of postoperative pancreatic fistula were analyzed by univariate and multivariate Logistic regression. Results:All patients successfully completed tumor enucleation without conversion to laparotomy. The operation time was (183.5±67.3)minutes(range:90 to 410 minutes). Twelve patients(20.0%) underwent stent placement and pancreatic duct repair during operation. The removal time of abdominal drainage tube after operation was (24.7±22.9)days(range:2 to 113 days). The tumor diameter in the robotic group was larger than that in the laparoscopic group((3.5±0.9)cm vs. (2.9±0.7)cm, t=-2.825, P=0.006). The incidences of postoperative biochemical fistula and grade B pancreatic fistula were 20.0%,22.9% and 36.0%,51.4%,respectively(χ2=2.289, P=0.318). There were no grade C pancreatic fistula,lymphatic fistula,biliary fistula,delayed gastric emptying,secondary operation and perioperative death in both groups. Multivariate logistic regression analysis was performed on the occurrence of clinically related pancreatic fistula(above grade B). The results showed that the increase of body mass index( OR=1.285,95% CI:1.053 to 1.569, P=0.014),the larger diameter of the tumor( OR=3.703,95% CI:1.465 to 9.360, P=0.006) and intraoperative pancreatic duct repair( OR=7.889,95% CI:1.471 to 42.296, P=0.016) were independent risk factors,whereas robotic surgery( OR=0.168,95% CI:0.036 to 0.796, P=0.025) was a protective factor. No case of pancreatin dependent dyspepsia and new onset diabetes mellitus was observed. Conclusions:Minimally invasive tumor enucleation is feasible in the treatment of benign and low-grade pancreatic tumors. The incidence of pancreatic fistula is high in the short term after operation,but serious complications are rare. The robot assisted system can reduce the risk of postoperative pancreatic fistula and has more advantages in dealing with larger diameter tumors because of clearer surgical vision and more accurate operation.
9.Minimally invasive enucleation for benign and low-grade malignant pancreatic tumors: an analysis of 60 cases
Mengqi LIU ; Wensheng LIU ; Zheng LI ; Qifeng ZHUO ; Shunrong JI ; Wenyan XU ; Yihua SHI ; Xianjun YU ; Xiaowu XU
Chinese Journal of Surgery 2022;60(7):674-679
Objective:To investigate the safety and feasibility of minimally invasive pancreatic tumor enucleation.Methods:The clinicopathological data of 60 patients with minimally invasive pancreatic tumor enucleation admitted to the Department of Pancreatic Surgery of Fudan University Cancer Center from November 2019 to August 2021 were retrospectively analyzed. There were 17 males and 43 females,with age of (50.0±13.2)years(range: 23 to 73 years). Tumors were located in the head of pancreas in 40 cases(66.7%),neck and tail of pancreas in 20 cases(33.3%). Patients were divided into robotic group( n=25) and laparoscopic group( n=35) according to surgical methods. The measurement data were compared by t-test or Mann-Whitney U test, and the categorical data were compared by χ 2 test or Fisher exact probability method. The influencing factors of postoperative pancreatic fistula were analyzed by univariate and multivariate Logistic regression. Results:All patients successfully completed tumor enucleation without conversion to laparotomy. The operation time was (183.5±67.3)minutes(range:90 to 410 minutes). Twelve patients(20.0%) underwent stent placement and pancreatic duct repair during operation. The removal time of abdominal drainage tube after operation was (24.7±22.9)days(range:2 to 113 days). The tumor diameter in the robotic group was larger than that in the laparoscopic group((3.5±0.9)cm vs. (2.9±0.7)cm, t=-2.825, P=0.006). The incidences of postoperative biochemical fistula and grade B pancreatic fistula were 20.0%,22.9% and 36.0%,51.4%,respectively(χ2=2.289, P=0.318). There were no grade C pancreatic fistula,lymphatic fistula,biliary fistula,delayed gastric emptying,secondary operation and perioperative death in both groups. Multivariate logistic regression analysis was performed on the occurrence of clinically related pancreatic fistula(above grade B). The results showed that the increase of body mass index( OR=1.285,95% CI:1.053 to 1.569, P=0.014),the larger diameter of the tumor( OR=3.703,95% CI:1.465 to 9.360, P=0.006) and intraoperative pancreatic duct repair( OR=7.889,95% CI:1.471 to 42.296, P=0.016) were independent risk factors,whereas robotic surgery( OR=0.168,95% CI:0.036 to 0.796, P=0.025) was a protective factor. No case of pancreatin dependent dyspepsia and new onset diabetes mellitus was observed. Conclusions:Minimally invasive tumor enucleation is feasible in the treatment of benign and low-grade pancreatic tumors. The incidence of pancreatic fistula is high in the short term after operation,but serious complications are rare. The robot assisted system can reduce the risk of postoperative pancreatic fistula and has more advantages in dealing with larger diameter tumors because of clearer surgical vision and more accurate operation.
10.Generated SecPen_NY-ESO-1_ubiquitin-pulsed dendritic cell cancer vaccine elicits stronger and specific T cell immune responses.
Yunkai YANG ; Xiaohan GUO ; Bo HU ; Peng HE ; Xiaowu JIANG ; Zuohuan WANG ; Huaxing ZHU ; Lina HU ; Minghua YU ; Meiqing FENG
Acta Pharmaceutica Sinica B 2021;11(2):476-487
Dendritic cell-based cancer vaccines (DC vaccines) have been proved efficient and safe in immunotherapy of various cancers, including melanoma, ovarian and prostate cancer. However, the clinical responses were not always satisfied. Here we proposed a novel strategy to prepare DC vaccines. In the present study, a fusion protein SNU containing a secretin-penetratin (SecPen) peptide, NY-ESO-1 and ubiquitin was designed and expressed. To establish the DC vaccine (DC-SNU), the mouse bone marrow-derived DCs (BMDCs) were isolated, pulsed with SNU and maturated with cytokine cocktail. Then peripheral blood mononuclear cells (PBMCs) from C57BL/6 mice inoculated intraperitoneally with DC-SNU were separated and cocultured with MC38/MC38

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